Evidence map›Paper›PMID 39276004›Full record

ArticleProtein science : a publication of the Protein Society2024

Substrate selectivity and inhibition of the human lysyl hydroxylase JMJD7.

Nurgül Bilgin, Anthony Tumber, Siddhant Dhingra, Eidarus Salah, Aziza Al-Salmy, Sandra Pinzón Martín, Yicheng Wang, Christopher J Schofield, Jasmin Mecinović

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In one paragraph

Article in Protein science : a publication of the Protein Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Substrate selectivity and inhibition of the human lysyl hydroxylase JMJD7.Protein science : a publication of the Protein Society · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Nurgül BilginDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
Anthony TumberChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
Siddhant DhingraChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
Eidarus SalahChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
Aziza Al-SalmyDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
Sandra Pinzón MartínDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
Yicheng WangChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
Christopher J SchofieldChemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford, UK.
Jasmin MecinovićDepartment of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.ORCID 0000-0002-5559-3822

Funding

Biotechnology and Biological Sciences Research Council BB/J003018/1Biotechnology and Biological Sciences Research Council BB/R000344/1Cancer Research UK C8717/A18245Lundbeck Foundation R344-2020-1051Novo Nordisk Fonden NNF21OC0072092Wellcome TrustWellcome Trust 106244/Z/14/Z
6 · The paper itself

Abstract

Jumonji-C (JmjC) domain-containing protein 7 (JMJD7) is a human Fe(II) and 2-oxoglutarate dependent oxygenase that catalyzes stereospecific C3-hydroxylation of lysyl-residues in developmentally regulated GTP binding proteins 1 and 2 (DRG1/2). We report studies exploring a diverse set of lysine derivatives incorporated into the DRG1 peptides as potential human JMJD7 substrates and inhibitors. The results indicate that human JMJD7 has a relatively narrow substrate scope beyond lysine compared to some other JmjC hydroxylases and lysine-modifying enzymes. The geometrically constrained (E)-dehydrolysine is an efficient alternative to lysine for JMJD7-catalyzed C3-hydroxylation. γ-Thialysine and γ-azalysine undergo C3-hydroxylation, followed by degradation to formylglycine. JMJD7 also catalyzes the S-oxidation of DRG1-derived peptides possessing methionine and homomethionine residues in place of lysine. Inhibition assays show that DRG1 variants possessing cysteine/selenocysteine instead of the lysine residue efficiently inhibit JMJD7 via cross-linking. The overall results inform on the substrate selectivity and inhibition of human JMJD7, which will help enable the rational design of selective small-molecule and peptidomimetic inhibitors of JMJD7.

Indexed as

Jumonji Domain-Containing Histone DemethylasesEnzyme InhibitorsHumansHydroxylationLysineSubstrate SpecificityEnzyme InhibitorsJumonji Domain-Containing Histone DemethylasesKDM6B protein, humanLysinebiocatalysisDRG1enzymologyJMJD7 hydroxylaselysineoxidation

Identifiers

PMID39276004
PMCPMC11400632

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.